Swimmers and divers throughout the world are familiar with the stinging organisms of the oceans, such as jellyfish, sea anemone and coral. Jellyfish stings, although seldom fatal, are a major public-health problem. Lotan et al. (1992) Marine Biology 112:237–242; Lotan et al. (1994) Marine Ecology Progress Series 109:59–65. In the summer months, it is estimated that over 500,000 swimmers and divers in the Chesapeake Bay area and 200,00 persons in Florida are stung by jellyfish, mainly by “sea nettles,” the common name of Chrysaora quinquecirrha. Burnett et al. (1992) MMI 41(6):509–513. Similarly, between the months of March and August in Florida, one in four bathers are stung and more than 10,000 persons require emergency medical treatment for pruritic eruptions caused by contact with jellyfish larvae known as “sea lice.” Tomchik el al. (1993) JAMA 269(13):1669–1672.
The members of the phylum Cnidaria (e.g., jellyfish, sea anemone and coral) and the phylum Myxozoa are all equipped with stinging subcellular organelles known as nematocysts, cnidocysts, or polar capsules. The nematocysts are located in specialized cells (nematocytes) and consist of capsules each containing a condensed tubule with potent toxins and threads. When nematocysts discharge, the tubule penetrates its target organism and releases its toxins. The threads arrayed on the tubule enhance the anchoring and attachment of the nematocyst tubule to its target. Nematocysts are involved in target recognition, toxin delivery, infection and attachment.
All members of the phyla Cnidaria and Myxozoa contain nematocysts of varying sizes, shapes and types Mariscal, pp. 129–178, “Nematocysts” in COELENTERATE BIOLOGY: REVIEWS AND NEW PERSPECTIVES, eds. Muscatine and Lenhoff (Academic Press, New York, 1974). These different types of cnidocysts function in diverse biological roles including capture of prey, toxin delivery, recognition, attachment, adherence and infection. (see, e.g., Tardent (1995); Bioessays 17(4):351–362; Lotan et al. (1995) Nature 375:4A56; Lotan et al. (1996) Expt'l Zool. 275:444–45 1; Lotan (1996) et al., pp. 132–145, “Toxicology and ecology and the Mediterranean jellyfish Rhopileim nomadica” in BIOCHEMICAL ASPECTS OF MARINE PHARMACOLOGY, eds. Lazarovici et al. (Alaken, Inc., Fort Collins, Colo., 199Q; Spaulding (1972) Biol. Bull. 143:440–453; Holstein and Tardent (1984) Science 223:830–833 and Mariscal, supra. Although best known for their stinging capabilities, nematocysts also play a key role in recognition, attachment and infection. For example, parasites from the phylum Myxozoa use nematocysts (polar capsules) to recognize and infect their hosts. El-Matbouli et al. (1995) J. Fish Biol. 46:919–935 and Yokoyama et al. (1995) Diseases Aquatic Organ. 21:7–11.
The main body of the nematocyte cell consists of a dense capsule, the nematocyst, within which is a highly folded eversible tubule. Discharge (eversion) of this tubule is driven by the build up of a high internal hydrostatic pressure of approximately 150 atmospheres within the capsule. The eversion of the internally folded tubule occurs within 3 microseconds at accelerations of up to 40,000×g, one of the most rapid mechanical events in cell biology.
The nematocyte can be sub-divided into 3 morphological compartments with different functional entities: the capsule lumen and wall, the tubule and the sensory organelles. The capsule wall and lumen are the main components involved in developing the driving force for nematocyst discharge. The tension on the inner capsule wall during nematocyst discharge reaches up to 375 MPa. Holstein (1994) Science 265:402–404. The strong capsule wall is highly permeable to water with a pore size of 600 Dalton. Within the resting nematocyst capsule, concentrations of up to 0.5 M of cations such as Ca++, Mg++ or K+ can be found. (see, e.g., Tardent, supra; Lubbock et al. (1981) PNAS 78(6):3624–3628; Godknecht et al. (1988) Marine Biology 100:83–92; Lubbock and Amos (1981) Nature 290(5806):500–501; Weber (1989) Int. J. Biochem. 184:465–476; Hidaka (1993) Biol. Bull. 184:97–104 and Gerke (1991) Hydrobiologia 216/217:661–669 for discussions of cations and nematocysts). The anionic counterparts are represented by poly-.gamma.-L-glutamatic acid (PGA) in varying degrees of polymerization. During nematocyst discharge, an extreme increase in internal capsule osmotic pressure occurs due to the influx of water. It has been suggested that the influx of water into the capsule is mediated by an internal release of the cations, such as Ca++ in sea anemone or K+ in hydra normally combined with PGA. This osmotic pressure is translated into hydrostatic pressure causing the eruption and then evagination of the tubule from the nematocyst capsule (discharge). After the nematocyst discharge, the internal cation concentration of the capsule is dissolved into the surrounding fluids.
The second compartment of the nematocyst is a highly condensed eversible tubule. This tubule serves the main role in nematocyte biological function, namely, the interaction or delivery of substances from the cnidarian or myxozoan into its target. The tubule, which is 200–850 μm when elongated, is twisted more than a hundred times around its axis and is packed into the 3–10 Jim diameter of the nematocyst. Godknecht & Tardent (1988) Marine Biol. 100:83–92. Hollow barbs, arrayed on the inner surface of the tubule, become everted during discharge and play an important role in the penetration and anchoring of the tubule into its prey. Toxins, contained on the outer surface before discharge, are delivered through the barbs after the nematocyst is anchored. Lotan et al. (1995), supra.
In sum, nematocysts provide an effective method of delivering a substance deep into the target. Because nematocysts are able to penetrate their target so efficiently, it is difficult to remove them or to treat after the toxin has penetrated. Conventionally, nematocyst stings have been treated with antidotes such as steroids, aluminum sulfate/surfactant and antihistamines. Tomchik, supra.
Since post-sting treatments for nematocyst stings are often unsatisfactory, the search for ways to prevent nematocyst discharge has been ongoing. The most often prescribed method of preventing jellyfish stings is to avoid any contact with the nematocysts. Tomchik, supra. However, in the case of microscopic larvae, this often means foregoing all ocean activities during the months of high incidence, (e.g., March through August in Florida). It would, therefore, be useful to have a means for inhibiting nematocyst discharge even when contact does occur.
Australian patent application 67563/94 (WO 94117779) discloses topical hydrodispersion preparations that are reported to be effective in preventing nematocyst discharge as measured by scanning electron microscopy (SEM). The formulations contain inorganic micropigments incorporated into the lipid phase of the hydrodispersion and an optional UV filtering substance and are essentially free of emulsifiers.
Lubbock (1979) J. Exp. Biol. 83:283–292 describes how proteinaceous compounds tend to induce a stronger response leading to nematocyst discharge in sea anemones than either polysaccharides or lipids. The authors could determine no simple recognition basis and speculated that the process of nematocyst discharge was complex. Lubbock and Amos, supra, disclose that isolated nematocyst capsules do not discharge in 50 mM CaCl2. The authors report that inhibition of nematocyst discharge occurs only if a solute that cannot rapidly penetrate the capsule wall is used, for example, high molecular weight polyethylene glycol. Thus, calcium in the surrounding environment may stabilize nematocysts because it reduces the differential between the calcium concentration outside and inside the capsule. Normally, the calcium concentration inside the nematocyst capsule is approximately 600 mM. Normal calcium concentration in sea water is around 7 mM, about 100-fold less than inside the capsule. Thus, increasing the calcium concentration outside the capsule to 50 mM reduces the differential to around 10 fold and may be involved in inhibiting nematocyst discharge.
Heeger et al. (1992) Marine Biology 113:669–678 tested the ability of three commercially available sunscreen lotions to inhibit jellyfish nematocyst discharge on samples of live human skin. Two of the three lotions were effective at reducing the number of nematocysts discharged. The authors concluded that glycerol and oil components of the lotions could be masking or suppressing the effects of natural stimuli of the skin, although even the lotion which did not inhibit nematocyst discharge contained these substances. Hartwick et al. (1980) Med. J. Australia 1:15–20 reported that commercial sting remedies do not inhibit nematocyst discharge.
Water soluble aluminum salts are known to serve as a method for treatment of bites, stings and wounds (Australian patent 475036, 513 983). The mechanisms of the action of aluminum salts in relation to relief of bites or stings is not clear, and it was suggested that the aluminum ion denatures venom, toxins and other stinging substances which may be the pain-causing agents. A composition for treatment of venomous bites and stings was developed by Douglas Henderson (U.S. Pat. No. 2,110,534). This waterproof composition contains concentrations of 13%–56% of aluminum salts and Methyl Eugenol and was found to be effective when applied topically against stinging from Bluebottle (Portuguese Man-o-War). The composition gave limited protection against Box jellyfish (Chronex fleckeri) stings.
Santoro et al (1991) J. Exp. Biol. 156, 173–185 demonstrated that induction of nematocysts discharge in the Sea anemone is Ca++ dependent. Aiptasia Mutabilis acontial filament was incubated in the Ca++-free artificial seawater (ASW) and the potential nematocycsts discharge was tested. Exposing the tentacles to several inducers of nematocyst discharge did not result in nematocyst activation. Nematocyst activation was resumed when 10 mM of Ca++ was introduced into the ASW medium. For understanding the role of Ca++ in nematocyst activation, several Ca++ channel inhibitors were applied to the tentacles. It was shown that incubation of sea anemone acontial filament in seawater medium containing 2 mM LaCl3, CoCl2, inactivates nematocyst discharge.
Salleo et al (1994) J. Exp. Biol. 187, 201–206 demonstrated that the Ca++ channel inhibitor Gd+3 applied through a gelatin probe, prevents discharge of nematocyte batteries in the oral arms of Pelagia nociluca. 
Since nematocyst stings present a major public health problem, especially in the summer months, the search for ways to prevent nematocyst discharge has been ongoing. It would, therefore, be useful to develop efficient methods for inhibiting nematocyst discharge even when contact does occur.